Ablation of oligodendrogenesis in adult mice alters brain microstructure and activity independently of behavioral deficits.

Oligodendrocytes continue to differentiate from their precursor cells even in adulthood, a process that can be modulated by neuronal activity and experience. Previous work has indicated that conditional ablation of oligodendrogenesis in adult mice leads to learning and memory deficits in a range of behavioral tasks. The current study replicated and re-evaluated evidence for a role of oligodendrogenesis in motor learning, using a complex running wheel task.

Attenuates Expression and Affects Alternative Splicing of a Subset of p53-Regulated Genes.

Background: Loss of the p53-inducible in p53-proficient CRC cell lines results in increased sensitivity to DNA-damaging chemotherapeutics. Here, we comprehensively analyze how affects the p53-induced transcriptional program.

Methods: Using a CRISPR/Cas9-approach, we deleted the p53 binding site in the promoter of SW480 colorectal cancer cells and subjected them to RNA-Seq analysis after the activation of ectopic p53.

Impacts of repeated social defeat on behavior and the brain in a cichlid fish.

Social defeat is a powerful experience leading to drastic changes in physiology and behavior, many of which are negative. For example, repeated social defeat in vertebrates results in reduced reproductive success, sickness and behavioral abnormalities that threaten individual survival and species persistence. However, little is known about what neural mechanisms are involved in determining whether an individual is resilient or susceptible to repeated social defeat stress.

Oligodendrocyte dynamics dictate cognitive performance outcomes of working memory training in mice.

Previous work has shown that motor skill learning stimulates and requires generation of myelinating oligodendrocytes (OLs) from their precursor cells (OLPs) in the brains of adult mice. In the present study we ask whether OL production is also required for non-motor learning and cognition, using T-maze and radial-arm-maze tasks that tax spatial working memory. We find that maze training stimulates OLP proliferation and OL production in the medial prefrontal cortex (mPFC), anterior corpus callosum (genu), dorsal thalamus and hippocampal formation of adult male mice; myelin sheath formation is also stimulated in the genu.

CRISPR/Cas9-mediated inactivation of miR-34a and miR-34b/c in HCT116 colorectal cancer cells: comprehensive characterization after exposure to 5-FU reveals EMT and autophagy as key processes regulated by miR-34.

The miR-34a and miR-34b/c encoding genes represent direct targets of the p53 transcription factor, and presumably mediate part of the tumor suppressive effects of p53. Here, we sought to determine their functional relevance by inactivating miR-34a and/or miR-34b/c using a CRISPR/Cas9 approach in the colorectal cancer (CRC) cell line HCT116. Concomitant deletion of miR-34a and miR-34b/c resulted in significantly reduced suppression of proliferation after p53 activation, enhanced migration, invasion and EMT, as well as reduced sensitivity to chemotherapeutics, increased stress-induced autophagic flux, decreased apoptosis and upregulation of autophagy-related genes after 5-FU treatment.

Effects of species, sex, and diet on thermal tolerance of Aedes aegypti and Culex quinquefasciatus (Diptera: Culicidae).

Thermal tolerance greatly influences the geographic distribution, seasonality, and feeding habits of mosquitoes; this study aimed to examine the impacts of species, sex, and diet on thermal tolerance in mosquitoes. We found that Culex quinquefasciatus was inherently significantly more cold tolerant than Aedes aegypti, while Ae. aegypti had improved heat tolerance compared to Cx.

c-MYC-Induced AP4 Attenuates DREAM-Mediated Repression by p53.

Background: The deregulated expression of the c-MYC oncogene activates p53, which is presumably mediated by ARF/INK4, as well as replication-stress-induced DNA damage. Here, we aimed to determine whether the c-MYC-inducible AP4 transcription factor plays a role in this context using a genetic approach.

Methods: We used a CRISPR/Cas9 approach to generate - and/or -deficient derivatives of MCF-7 breast cancer cells harboring an ectopic, inducible c-MYC allele.

Analysis of the p53/microRNA Network in Cancer.

MicroRNAs (miRNAs) are important components of the signaling cascades that mediate and regulate tumor suppression exerted by p53. This review illustrates some of the main principles that underlie the mechanisms by which miRNAs participate in p53's function and how they were identified. Furthermore, the current status of the research on the connection between p53 and miRNAs, as well as alterations in the p53/miRNA pathways found in cancer will be summarized and discussed.

In vivo PDX CRISPR/Cas9 screens reveal mutual therapeutic targets to overcome heterogeneous acquired chemo-resistance.

Resistance towards cancer treatment represents a major clinical obstacle, preventing cure of cancer patients. To gain mechanistic insights, we developed a model for acquired resistance to chemotherapy by treating mice carrying patient derived xenografts (PDX) of acute lymphoblastic leukemia with widely-used cytotoxic drugs for 18 consecutive weeks. In two distinct PDX samples, tumors initially responded to treatment, until stable disease and eventually tumor re-growth evolved under therapy, at highly similar kinetics between replicate mice.

mediates enhancement of intestinal tumorigenesis caused by inactivation of .

The CSF1 receptor (CSF1R) encoding mRNA represents a direct target of miR-34a. However, the relevance of the suppression of by miR-34a for intestinal tumor suppression mediated by the p53/miR-34a pathway has remained unknown. Here, mice with intestinal-epithelial cell (IEC)-specific deletions of showed increased formation of adenomas and decreased survival, whereas deletion of decreased adenoma formation and increased survival.

Transgenerational effects of parental crude oil exposure on the morphology of adult Fundulus grandis.

The current study involved exposing adult F0 Gulf killifish (Fundulus grandis) to Macondo-252 oil for 36 to 44 days and assessing the effects of this oiling on the swimming performance and morphology in two generations of progeny reared in clean water. Following exposure to oil, the F0 fish were used as broodstock to generate four lineages of F1 fish using a full-matrix mating design derived from the gametes of clean and oil-exposed parents. Later, the four lineages of F1 fish were used as broodstock to create an F2 generation of the same four lineages.

AP4 suppresses DNA damage, chromosomal instability and senescence via inducing MDC1/Mediator of DNA damage Checkpoint 1 and repressing MIR22HG/miR-22-3p.

Background: AP4 (TFAP4) encodes a basic helix-loop-helix leucine zipper (bHLH-LZ) transcription factor and is a direct target gene of the oncogenic transcription factor c-MYC. Here, we set out to determine the relevance of AP4 in human colorectal cancer (CRC) cells.

Methods: A CRISPR/Cas9 approach was employed to generate AP4-deficient CRC cell lines with inducible expression of c-MYC.

Intraspecific Growth and Aflatoxin Inhibition Responses to Atoxigenic : Evidence of Secreted, Inhibitory Substances in Biocontrol.

The fungus infects corn, peanut, and cottonseed, and contaminates seeds with acutely poisonous and carcinogenic aflatoxin. Aflatoxin contamination is a perennial threat in tropical and subtropical climates. Nonaflatoxin-producing isolates (atoxigenic) are deployed in fields to mitigate aflatoxin contamination.

Targeting the Mitotic Kinesin KIF18A in Chromosomally Unstable Cancers: Hit Optimization Toward an In Vivo Chemical Probe.

Chromosomal instability (CIN) is a hallmark of cancer that results from errors in chromosome segregation during mitosis. Targeting of CIN-associated vulnerabilities is an emerging therapeutic strategy in drug development. KIF18A, a mitotic kinesin, has been shown to play a role in maintaining bipolar spindle integrity and promotes viability of CIN cancer cells.

Genome-Wide Analysis of c-MYC-Regulated mRNAs and miRNAs and c-MYC DNA-Binding by Next-Generation Sequencing.

The c-MYC oncogene is activated in ~50% of all tumors and its product, the c-MYC transcription factor, regulates numerous processes, which contribute to tumor initiation and progression. Therefore, the genome-wide characterization of c-MYC targets and their role in different tumor entities is a recurrent theme in cancer research. Recently, next-generation sequencing (NGS) has become a powerful tool to analyze mRNA and miRNA expression, as well as DNA binding of proteins in a genome-wide manner with an extremely high resolution and coverage.

Erratum: Wagner, A.E., et al. SP8 Promotes an Aggressive Phenotype in Hepatoblastoma via FGF8 Activation. 2020, , 2294.

Two contributors' names were missing in the original version of the authorship of the paper [...

Comparing multiple comparisons: practical guidance for choosing the best multiple comparisons test.

Multiple comparisons tests (MCTs) include the statistical tests used to compare groups (treatments) often following a significant effect reported in one of many types of linear models. Due to a variety of data and statistical considerations, several dozen MCTs have been developed over the decades, with tests ranging from very similar to each other to very different from each other. Many scientific disciplines use MCTs, including >40,000 reports of their use in ecological journals in the last 60 years.

Sarek: A portable workflow for whole-genome sequencing analysis of germline and somatic variants.

Whole-genome sequencing (WGS) is a fundamental technology for research to advance precision medicine, but the limited availability of portable and user-friendly workflows for WGS analyses poses a major challenge for many research groups and hampers scientific progress. Here we present Sarek, an open-source workflow to detect germline variants and somatic mutations based on sequencing data from WGS, whole-exome sequencing (WES), or gene panels. Sarek features (i) easy installation, (ii) robust portability across different computer environments, (iii) comprehensive documentation, (iv) transparent and easy-to-read code, and (v) extensive quality metrics reporting.

Point spread function in interferometric scattering microscopy (iSCAT). Part I: aberrations in defocusing and axial localization.

Interferometric scattering (iSCAT) microscopy is an emerging label-free technique optimized for the sensitive detection of nano-matter. Previous iSCAT studies have approximated the point spread function in iSCAT by a Gaussian intensity distribution. However, recent efforts to track the mobility of nanoparticles in challenging speckle environments and over extended axial ranges has necessitated a quantitative description of the interferometric point spread function (iPSF).

Characterization of a p53/miR-34a/CSF1R/STAT3 Feedback Loop in Colorectal Cancer.

Background & Aims: The miR-34a gene is a direct target of p53 and is commonly silenced in colorectal cancer (CRC). Here we identified the receptor tyrosine kinase CSF1R as a direct miR-34a target and characterized CSF1R as an effector of p53/miR-34a-mediated CRC suppression.

Methods: Analyses of TCGA-COAD and three other CRC cohorts for association of mRNA expression and signatures with patient survival and molecular subtypes.

High throughput barcoding method for genome-scale phasing.

The future of human genomics is one that seeks to resolve the entirety of genetic variation through sequencing. The prospect of utilizing genomics for medical purposes require cost-efficient and accurate base calling, long-range haplotyping capability, and reliable calling of structural variants. Short-read sequencing has lead the development towards such a future but has struggled to meet the latter two of these needs.

Chromosomal genome assembly of the ethanol production strain CBS 11270 indicates a highly dynamic genome structure in the yeast species Brettanomyces bruxellensis.

Here, we present the genome of the industrial ethanol production strain Brettanomyces bruxellensis CBS 11270. The nuclear genome was found to be diploid, containing four chromosomes with sizes of ranging from 2.2 to 4.